CYP26C1

protein-coding

cytochrome P450 family 26 subfamily C member 1, the group of Cytochrome P450 family 26

Gene summary

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This enzyme is involved in the catabolism of all-trans- and 9-cis-retinoic acid, and thus contributes to the regulation of retinoic acid levels in cells and tissues. This gene is adjacent to a related gene on chromosome 10q23.33. [provided by RefSeq, Jul 2008]

MANE transcript

NM_183374.3

Inheritance

ClinVar variants

P:6U:96B:22

Top phenotype

Focal facial dermal dysplasia 4

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr10:93,060,798-93,069,540

External References & Databases

Ensembl (ENSG00000187553)

Transcript & Mutation Effects

hg38 • Region Span ~8.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

focal facial dermal dysplasia type IVLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013997

Submitter: Ambry Genetics

focal facial dermal dysplasia type IVSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013997

Submitter: Labcorp Genetics (formerly Invitae)

focal facial dermal dysplasia type IVSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013997

Submitter: Orphanet

Clinical Genomic Database (CGD)

Focal facial dermal dysplasia 4AR

Manifestation: Craniofacial; Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 16530710; 23161670

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP26C1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 99

not providedTotal: 18

CYP26C1-related disorderTotal: 7

Focal facial dermal dysplasia type IVTotal: 7

Optic nerve hypoplasiaTotal: 2

Anophthalmia-microphthalmia syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_183374.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				11 clinvar	2 clinvar	13
missense		1 clinvar	95 clinvar	7 clinvar	2 clinvar	105
nonsense		2 clinvar				2
start loss						0
frameshift	1 clinvar	1 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	1	5	96	18	4	124

Highest pathogenic variant AF is 0.0005741553

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_183374.3	RefSeq	NP_899230.2	6	MANE Select
ENST00000651965.1	Ensembl	ENSP00000498424.1	6	MANE Select
ENST00000624358.3	Ensembl	ENSP00000485098.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cyp26c1	Danio rerio	Structure: pharyngeal arch Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

cyp26c1

Danio rerio

Structure: pharyngeal arch

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinol metabolism - Homo sapiens (human)
Oxidation by Cytochrome P450
Metapathway biotransformation Phase I and II
Signal Transduction
Phase I - Functionalization of compounds

Biological Process

vitamin metabolic process
central nervous system development
anterior/posterior pattern specification
neural crest cell development
sterol metabolic process

Molecular Function

retinoic acid binding
iron ion binding
retinoic acid 4-hydroxylase activity
heme binding

Cellular Component

endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000285949
Coding exons: 6
Length: 7434
Individuals with no LoFs: 125150
Homozygous LoFs: 1
Heterozygous LoFs: 565
Defined: 125716
p: 0.00225

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0585	274	277	0.990	0.0000136	3219
Missense (PolyPhen)		120	117.65	1.0199		1409
Synonymous	1.54	109	132	0.829	0.00000668	1181
Loss of Function	1.97	7	15.3	0.457	7.17e-7	170

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00055	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0012	0.0011	notable
Finnish	0.0072	0.0072	notable
European (Non-Finnish)	0.0032	0.0032	notable
South Asian	0.000033	0.000033	rare
Other	0.0023	0.0023	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in retinoic acid metabolism. Acts on retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA (preferred substrate).;
Disease: DISEASE: Focal facial dermal dysplasia 4 (FFDD4) [MIM:614974]: A form of focal facial dermal dysplasia, a group of developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. Skin defects occur at the sites of facial fusion during embryogenesis, with temporal lesions situated at the junction between the frontonasal and maxillary facial prominences, and preauricular lesions at the meeting point of the maxillary and mandibular prominences. The ectodermal lesions show consistent histologic abnormalities: atrophy and flattening of the epidermis, replacement of the dermis by loose connective tissue, reduced levels of fragmented elastic tissue and absence of the subcutaneous tissues and adnexal structures. FFDD4 is characterized by isolated, preauricular skin lesions. {ECO:0000269|PubMed:23161670}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.281

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium